A mass spectrometry (MS) system in general includes an ion source for ionizing components of a sample of interest, a mass analyzer for separating the ions based on their differing mass-to-charge ratios (or m/z ratios, or more simply “masses”), an ion detector for counting the separated ions, and electronics for processing output signals from the ion detector as needed to produce a user-interpretable mass spectrum. Typically, the mass spectrum is a series of peaks indicative of the relative abundances of detected ions as a function of their m/z ratios. The mass analyzer may be a time-of-flight (TOF) analyzer. Ions produced by the ion source are transmitted into the TOF analyzer where they are mass-resolved based on their flight times to the detector.
An important performance criterion of a mass analyzer is its mass resolution or resolving power. A TOF analyzer is often considered to have limited mass resolution in comparison to certain other types of mass analyzers. Several factors or effects contribute to the limited mass resolution of a TOF analyzer. Major factors include the width of the ion detector pulse, peak broadening due to voltage instability, mechanical misalignments, lack of detector flatness (surface unevenness), pulser jitter (the ion pulser of the TOF analyzer), scattering on grids utilized in the TOF analyzer, and turn-around time (the spread in ion arrival at the detector due to ions entering the pulser at different angles, resulting in some ions having a velocity component opposite to the direction of pulsed extraction). One could improve the mass resolution if at least one of these factors (preferably the factor that contributes the most) is reduced. The factors may be conceptually divided into two groups, which will be referred to herein as group I factors and group II factors. Group I factors include factors that affect all ions in a similar fashion during one TOF period (i.e., one TOF cycle, or “transient”). Examples of group I factors include low-frequency high-voltage (HV) instability, mechanical vibration, and pulser jitter. Group II factors include factors that affect each ion in a transient in an intrinsically different way. Examples of group II factors include turn-around time and detector surface unevenness.
If one were to examine the spectrum contained in a given transient, the shifts of ion peaks in it due to group I factors would be correlated in the sense that all peaks due to group I factors would appear to be shifted in the same direction, whereas the shifts of ion peaks due to group II factors would not be correlated. In the present disclosure, it is proposed that if a transient-level correction could be made based on the correlation of the shifts due to group I factors, the resulting peak width could be reduced by a significant amount and the mass resolution could be increased accordingly.
Techniques for peak correction known in the art rely on correction of peak position based on the position of the peaks of reference mass ions (ions produced from reference compounds, or calibrants, of known structure, composition and m/z ratios) observed in the spectra. Typically, the correction is performed after a complete spectrum is acquired (i.e., the accumulation of data from multiple transients processed in the TOF analyzer). The known techniques may be effective in compensating for variations in the system parameters that transpire over relatively long periods of time, for example, a period of over 100 ms and typically over several seconds. As a result, correcting peak position according to known techniques may improve mass accuracy, but not mass resolution. In other known techniques, peak data may be corrected based on a single transient digitization to reduce the width of the detector response, which may lead to some improvement in mass resolution. However, these latter techniques do nothing to compensate for the drift of an instrument parameter between individual transients.
Therefore, there is a need for providing a solution for implementing peak corrections at the transient level, and for correcting multiple transients, so as to compensate for various sources of instrument instabilities, including those occurring over short time periods.